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Journal of Managed Care & Specialty... Dec 2023People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population.
OBJECTIVE
To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS.
METHODS
MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs.
RESULTS
We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers.
CONCLUSIONS
The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.
Topics: Humans; Bone Density; Prospective Studies; Anticonvulsants; Anti-Anxiety Agents; Retrospective Studies; Cross-Sectional Studies; Glucocorticoids; Multiple Sclerosis; Fractures, Bone; Antidepressive Agents; Immunologic Factors
PubMed: 38058136
DOI: 10.18553/jmcp.2023.29.12.1331 -
Reviews in Medical Virology Nov 2023A number of different neurological complications have been reported following vaccination against the coronavirus disease 2019 (COVID-19). Electroencephalogram (EEG) is... (Review)
Review
A number of different neurological complications have been reported following vaccination against the coronavirus disease 2019 (COVID-19). Electroencephalogram (EEG) is one of the modalities used to evaluate the neurological complications of diseases. The aim of the present study was to identify the EEG changes in participants vaccinated against COVID-19. PubMed, Scopus, Web of Science, medRxiv, and Google Scholar were searched up to 1 September 2022, with terms related to COVID-19 vaccines, EEG, neurological signs/symptoms, or neurological disorders. All case reports and case series were included if the participants had received at least one dose of a COVID-19 vaccine and a post vaccination EEG report was also reported. We used the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for case reports and case series to appraise the methodological quality of the included studies. Thirty-one studies were included, which were comprised of 24 case reports and seven case series and a total of 36 participants. Generalised slowing and non-convulsive focal status epilepticus were the most common EEG findings post-COVID-19 vaccination. The most frequent symptoms were headache, fatigue, generalised weakness, and vomiting. In addition, the most common signs were encephalopathy, post-ictal phases, and confusion. Encephalitis, acute disseminated encephalomyelitis, and post-vaccinal encephalopathy were the most commonly diagnosed adverse events. Furthermore, most of the imaging studies appeared normal. The EEG reports mainly showed background slowing and epileptiform discharges, encephalitis, encephalopathies, and demyelinating disorders. Future studies with larger samples and more vaccine types may help to further unravel the potential neurological effects of COVID-19 vaccinations on recipients.
Topics: Humans; Brain Diseases; COVID-19; COVID-19 Vaccines; Electroencephalography; Encephalitis; Vaccination; Case Reports as Topic
PubMed: 37807809
DOI: 10.1002/rmv.2484 -
Multiple Sclerosis and Related Disorders Nov 2023The prevalence of depression in Multiple Sclerosis (MS) is common and negatively affects the quality of life of patients. The studies of the effect of remote forms of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence of depression in Multiple Sclerosis (MS) is common and negatively affects the quality of life of patients. The studies of the effect of remote forms of treatment conclude that it is a fairly easy process to carry out and with very good results for patients. Thus, the purpose of this systematic review and meta-analysis is to investigate randomized controlled trials on the effectiveness of remote forms of exercise and physiotherapy on the depressive symptoms of people with MS.
METHODS
A literature search was conducted in PubMed, Scopus, PsychInfo, SportDiscus, Web of Science and ResearchGate databases. The keywords for the search were: telerehabilitation, telecounseling, tele, telephone, physiotherapy, physical therapy, rehabilitation, therapeutic exercise, exercise, depression, depressive disorders, multiple sclerosis and MS. In addition, some inclusion and exclusion criteria were defined for the selection of the final studies, which were also evaluated with the PEDro scale for their quality.
RESULTS
Among the initial 176 studies found, 6 were included in the systematic review. The development of a remote individualized exercise program based on assessment, personal goals and daily life of the patient, as well as a program based on motor imagery training, showed beneficial effects on depression in people with MS, which are considered possibly equivalent to those of in-person intervention. Μeta-analysis revealed that remote exercise and physiotherapy programs are significantly more effective than control group interventions for the management of depression in people with MS (random effects model, Hedges' g = -0.41, 95%CI = -0.74,-0.09, SE = 0.17, p = 0.01). The sub-group analysis showed that studies that had chosen not to have their control group carry out any form of intervention had more significant outcomes than the others.
CONCLUSION
Through telephone communication or other electronic monitoring systems, can be achieved an effective treatment of people with depression and MS, based on exercise and physiotherapy. However, more studies are deemed necessary to find the most appropriately designed and therapeutic forms of remote intervention.
Topics: Humans; Depression; Quality of Life; Multiple Sclerosis; Exercise; Exercise Therapy; Physical Therapy Modalities
PubMed: 37844435
DOI: 10.1016/j.msard.2023.105067 -
Prosthetics and Orthotics International Aug 2023Foot-drop is one of the most diagnosed and physically limiting symptoms persons with multiple sclerosis (pwMS) experience. Clinicians prescribe ankle-foot orthosis (AFO)... (Meta-Analysis)
Meta-Analysis
Foot-drop is one of the most diagnosed and physically limiting symptoms persons with multiple sclerosis (pwMS) experience. Clinicians prescribe ankle-foot orthosis (AFO) and functional electrical stimulation (FES) devices to help alleviate the effects of foot drop, but it is unclear how their clinical and functional gait improvements compare given the user's level of disability, type of multiple sclerosis, walking environment, or desired physical activity. The research questions explored were what is the current state of AFO and FES research for pwMS? What are the prevailing research trends? What definitive clinical and functional device comparisons exist for pwMS? eight databases were systematically searched for relevant literature published between 2009 and 2021. The American Association of Orthotists and Prosthetists and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for systematic literature reviews were followed. A team of 3 researchers critically evaluated 17 articles that passed eligibility criteria. This review discusses the current state and trends of research, provides evidence statements on device effects, and recommends improvements for future studies. A meta-analysis would be informative, but study variability across the literature makes directly comparing AFO and FES device effects unreliable. This review contributes new and useful information to multiple sclerosis literature that can be used by both clinicians and researchers. Clinicians can use the provided insights to prescribe more effective, customized treatments, and other researchers can use them to evaluate and design future studies.
Topics: Humans; Foot Orthoses; Ankle; Multiple Sclerosis; Peroneal Neuropathies; Electric Stimulation Therapy; Peroneal Nerve; Gait; Electric Stimulation; Gait Disorders, Neurologic; Stroke
PubMed: 36701192
DOI: 10.1097/PXR.0000000000000190 -
Human Cell Jan 2024Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.
Topics: Humans; Multiple Sclerosis; Neurodegenerative Diseases; Myelin Sheath; Stem Cells; Oligodendroglia
PubMed: 37985645
DOI: 10.1007/s13577-023-01006-1 -
Biomedicine & Pharmacotherapy =... Aug 2023Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease, but it is one of the most common inflammatory neuropathies in the population. It is particularly common among patients with diabetes mellitus. This raises many problems, both with the differential diagnosis of diabetic and inflammatory neuropathy, as well as the choice of treatment. Intravenous immunoglobulin (IVIG) is one of the therapeutic options. There is evidence for the effectiveness of IVIG in treating about two-thirds of patients. However, no review has been published to date systematising studies evaluating the response to IVIG treatment in patients with CIDP and coexisting diabetes.
METHODS
The present study is based on the PRISMA statement and is registered at PROSPERO (CRD42022356180). The study included searches of the databases of MEDLINE, ERIC, CINAHL Complete, Academic Search Ultimate and Health Source: Nursing/Academic Edition, finally including seven original papers evaluating a total of 534 patients in the review. The main inclusion criteria were the presence of a group of patients with CIDP and comorbid diabetes in the study.
RESULTS
The systematic review showed a lower efficacy of IVIG treatment among patients with coexisting diabetes compared with idiopathic CIDP (61 % vs 71 %). In addition, the presence of conduction blocks on neurography and shorter disease duration proved to be significant factors improving response to treatment.
CONCLUSIONS
Current scientific data do not allow for strong recommendations on the choice of treatment for CIDP. A randomised, multicentre study evaluating the efficacy of different therapeutic approaches to this disease entity needs to be planned.
Topics: Humans; Immunoglobulins, Intravenous; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Infusions, Intravenous; Administration, Intravenous; Diabetes Mellitus; Multicenter Studies as Topic
PubMed: 37290187
DOI: 10.1016/j.biopha.2023.114974 -
European Journal of Medical Research Aug 2023Multiple Sclerosis (MS) is a chronic debilitating disease that targets the central nervous system. Globally it is estimated that 2.8 million people live with MS (2018)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Multiple Sclerosis (MS) is a chronic debilitating disease that targets the central nervous system. Globally it is estimated that 2.8 million people live with MS (2018) and as there is no known cure; therefore, identifying methods to increase a patient's quality of life (QoL) is of considerable importance. Non-pharmacological interventions are a viable and effective option to increase QoL in patients with MS, however, to date, the literature lacks a complete systematic review of these interventions.
METHODS
A literature search was conducted for studies published up until March 4th 2022 in Scopus, Web of Science, CINAHL Plus, The Cochrane Library, Medline, and Embase. Studies were included if they were randomized control trials (RCTs) assessing a non-pharmacological intervention in adults with MS and measured QoL using the MSQOL-54, SF-36 or MSQLI tools for at least two time points. Quality assessment of each study was completed as well as a review of publication bias. Where possible, meta-analysis was conducted using a random effects model and for other studies a qualitative synthesis was presented.
RESULTS
Thirty studies were included in the meta-analysis and eleven studies were summarized qualitatively. The pooled effects across all non-pharmacological interventions showed a modest improvement in both the physical and mental components of QoL, with a standardized mean difference (SMD) of 0.44 (95% CI 0.26-0.61) and 0.42 (95% CI 0.24-0.60), respectively. Non-pharmacological interventions based around a physical activity were found to be particularly effective in improving both the physical composite score (PCS) and mental composite score (MCS), with an SMD of 0.40 (95% CI 0.14-0.66) and 0.31 (95% CI 0.08-0.55), respectively. Interventions incorporating balance exercises presented a significant advantageous solution for improving QoL, with an SMD of 1.71 (95% CI 1.22, 2.20) and 1.63(95% CI 1.15-2.12) for PCS and MCS respectively.
CONCLUSIONS
This systematic review and meta-analysis identified that non-pharmacological interventions can be an effective method of improving QoL in patients with MS, especially modalities with a physical activity component and balance interventions.
Topics: Humans; Adult; Multiple Sclerosis; Central Nervous System; Quality of Life; Exercise; Randomized Controlled Trials as Topic
PubMed: 37608400
DOI: 10.1186/s40001-023-01185-5 -
The Cochrane Database of Systematic... Sep 2023Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects millions of people worldwide. The disease course varies greatly across individuals and many disease-modifying treatments with different safety and efficacy profiles have been developed recently. Prognostic models evaluated and shown to be valid in different settings have the potential to support people with MS and their physicians during the decision-making process for treatment or disease/life management, allow stratified and more precise interpretation of interventional trials, and provide insights into disease mechanisms. Many researchers have turned to prognostic models to help predict clinical outcomes in people with MS; however, to our knowledge, no widely accepted prognostic model for MS is being used in clinical practice yet.
OBJECTIVES
To identify and summarise multivariable prognostic models, and their validation studies for quantifying the risk of clinical disease progression, worsening, and activity in adults with MS.
SEARCH METHODS
We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews from January 1996 until July 2021. We also screened the reference lists of included studies and relevant reviews, and references citing the included studies.
SELECTION CRITERIA
We included all statistically developed multivariable prognostic models aiming to predict clinical disease progression, worsening, and activity, as measured by disability, relapse, conversion to definite MS, conversion to progressive MS, or a composite of these in adult individuals with MS. We also included any studies evaluating the performance of (i.e. validating) these models. There were no restrictions based on language, data source, timing of prognostication, or timing of outcome.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently screened titles/abstracts and full texts, extracted data using a piloted form based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS), assessed risk of bias using the Prediction Model Risk Of Bias Assessment Tool (PROBAST), and assessed reporting deficiencies based on the checklist items in Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD). The characteristics of the included models and their validations are described narratively. We planned to meta-analyse the discrimination and calibration of models with at least three external validations outside the model development study but no model met this criterion. We summarised between-study heterogeneity narratively but again could not perform the planned meta-regression.
MAIN RESULTS
We included 57 studies, from which we identified 75 model developments, 15 external validations corresponding to only 12 (16%) of the models, and six author-reported validations. Only two models were externally validated multiple times. None of the identified external validations were performed by researchers independent of those that developed the model. The outcome was related to disease progression in 39 (41%), relapses in 8 (8%), conversion to definite MS in 17 (18%), and conversion to progressive MS in 27 (28%) of the 96 models or validations. The disease and treatment-related characteristics of included participants, and definitions of considered predictors and outcome, were highly heterogeneous amongst the studies. Based on the publication year, we observed an increase in the percent of participants on treatment, diversification of the diagnostic criteria used, an increase in consideration of biomarkers or treatment as predictors, and increased use of machine learning methods over time. Usability and reproducibility All identified models contained at least one predictor requiring the skills of a medical specialist for measurement or assessment. Most of the models (44; 59%) contained predictors that require specialist equipment likely to be absent from primary care or standard hospital settings. Over half (52%) of the developed models were not accompanied by model coefficients, tools, or instructions, which hinders their application, independent validation or reproduction. The data used in model developments were made publicly available or reported to be available on request only in a few studies (two and six, respectively). Risk of bias We rated all but one of the model developments or validations as having high overall risk of bias. The main reason for this was the statistical methods used for the development or evaluation of prognostic models; we rated all but two of the included model developments or validations as having high risk of bias in the analysis domain. None of the model developments that were externally validated or these models' external validations had low risk of bias. There were concerns related to applicability of the models to our research question in over one-third (38%) of the models or their validations. Reporting deficiencies Reporting was poor overall and there was no observable increase in the quality of reporting over time. The items that were unclearly reported or not reported at all for most of the included models or validations were related to sample size justification, blinding of outcome assessors, details of the full model or how to obtain predictions from it, amount of missing data, and treatments received by the participants. Reporting of preferred model performance measures of discrimination and calibration was suboptimal.
AUTHORS' CONCLUSIONS
The current evidence is not sufficient for recommending the use of any of the published prognostic prediction models for people with MS in clinical routine today due to lack of independent external validations. The MS prognostic research community should adhere to the current reporting and methodological guidelines and conduct many more state-of-the-art external validation studies for the existing or newly developed models.
Topics: Adult; Humans; Prognosis; Multiple Sclerosis; Reproducibility of Results; Systematic Reviews as Topic; Disease Progression
PubMed: 37681561
DOI: 10.1002/14651858.CD013606.pub2 -
Magnetic Resonance Imaging Dec 2023Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS), namely the phenotype of the relapsing-remitting form, is the most common white matter disease and is mostly characterized by demyelination and inflammation, which lead to neurodegeneration and cognitive decline. Its diagnosis and monitoring are performed through conventional structural MRI, in which T2-hyperintense lesions can be identified, but this technique lacks sensitivity and specificity, mainly in detecting damage to normal appearing tissues. Models of diffusion-weighted MRI such as diffusion-tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) allow to uncover microstructural abnormalities that occur in MS, mainly in normal appearing tissues such as the normal appearing white matter (NAWM), which allows to overcome limitations of conventional MRI. DTI is the standard method used for modelling this kind of data, but it has limitations, which can be tackled by using more complex diffusion models, such as NODDI, which provides additional information on morphological properties of tissues. Although there are several studies in MS using both diffusion models, there is no formal assessment that summarizes the findings of both methods in lesioned and normal appearing tissues, and whether one is more advantageous than the other. Hence, this systematic review aims to identify what microstructural abnormalities are seen in lesions and/or NAWM in relapsing-remitting MS while using two different approaches to modelling diffusion data, namely DTI and NODDI, and if one of them is more appropriate than the other or if they are complementary to each other. The search was performed using PubMed, which was last searched on November 2022, and aimed at finding studies that either utilized both DTI and NODDI in the same dataset, or only one of the methods. Eleven articles were included in this review, which included cohorts with a relatively low sample size (total number of patients = 254, total number of healthy controls = 240), and patients with a moderate disease duration, all with relapsing-remitting MS. Overall, studies found decreased fractional anisotropy (FA), neurite density index (NDI) and orientation dispersion index (ODI), and increased mean, axial and radial diffusivities (MD, AD and RD, respectively) in lesions, when compared to contralateral NAWM and healthy controls' white matter. Compared to healthy controls' white matter, NAWM showed lower FA and NDI and higher MD, AD, RD, and ODI. Results from the included articles confirm that there is active demyelination and inflammation in both lesions and NAWM, as well as loss in neurites, and that structural damage is not confined to focal lesions, which is in concordance with histological findings and results from other imaging techniques. Furthermore, NODDI is suggested to have higher sensitivity and specificity, as seen by inspecting imaging results, compared to DTI, while still being clinically feasible. The use of biomarkers derived from such advanced diffusion models in clinical practice could imply a better understanding of treatment efficacy and disease progression, without relying on the manifestation of clinical symptoms, such as relapses.
Topics: Humans; Multiple Sclerosis; Diffusion Tensor Imaging; Diffusion Magnetic Resonance Imaging; White Matter; Brain; Neurites; Image Processing, Computer-Assisted
PubMed: 37775062
DOI: 10.1016/j.mri.2023.09.010 -
Scandinavian Journal of Medicine &... Jan 2024This systematic review evaluated the safety and efficacy of blood flow restriction exercise (BFRE) on skeletal muscle size, strength, and functional performance in... (Review)
Review
OBJECTIVES
This systematic review evaluated the safety and efficacy of blood flow restriction exercise (BFRE) on skeletal muscle size, strength, and functional performance in individuals with neurological disorders (ND).
METHODS
A literature search was performed in PubMed, CINAHL, and Embase. Two researchers independently assessed eligibility and performed data extraction and quality assessments.
ELIGIBILITY CRITERIA
Study populations with ND, BFRE as intervention modality, outcome measures related to safety or efficacy.
RESULTS
Out of 443 studies identified, 16 were deemed eligible for review. Three studies examined the efficacy and safety of BFRE, one study focused on efficacy results, and 12 studies investigated safety. Disease populations included spinal cord injury (SCI), inclusion body myositis (sIBM), multiple sclerosis (MS), Parkinson's disease (PD), and stroke. A moderate-to-high risk of bias was presented in the quality assessment. Five studies reported safety concerns, including acutely elevated pain and rating of perceived exertion levels, severe fatigue, muscle soreness, and cases of autonomic dysreflexia. Two RCTs reported a significant between-group difference in physical function outcomes, and two RCTs reported neuromuscular adaptations.
CONCLUSION
BFRE seems to be a potentially safe and effective training modality in individuals with ND. However, the results should be interpreted cautiously due to limited quality and number of studies, small sample sizes, and a general lack of heterogeneity within and between the examined patient cohorts.
Topics: Humans; Blood Flow Restriction Therapy; Multiple Sclerosis; Myalgia; Nervous System Diseases; Parkinson Disease
PubMed: 38268066
DOI: 10.1111/sms.14561